This application is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/US2015/016057, filed Feb. 16, 2015, which claims the priority benefit of United States Provisional Patent Application No. 61/940,339, filed Feb. 14, 2014, the entirety of which are incorporated herein by reference.
This invention was made with government support under grant number W81XWH-11-1-0002 awarded by the U.S. Department of the Army. The government has certain rights in the invention.
Field of the Invention
The present invention relates generally to the field of molecular biology and medicine. More particularly, it concerns methods of generating chimeric antigen receptors (CAR).
Description of Related Art
Adoptive T cell transfer is a promising therapeutic approach that may be used for the treatment of cancer. Adoptive T cell transfer involves isolating and expanding antigen-specific T cells that can selectively kill tumor cells. Generally, T cells are removed from a subject and cultured in vitro. A Chimeric Antigen Receptor (CARs) may be introduced into a T cell in vitro to direct the T cell, once re-introduced into the subject, to selectively kill tumor cells based on expression of an antigen (e.g., Wieczorek et al. 2013; Berry et al., 2013).
One problem associated with adoptive T cell transfer is that significant variability exists between which CAR may work more effectively in certain populations of patients, e.g., for treating a specific cancer. Due to the very large number of potential different CAR that could potentially be generated that might exhibit therapeutic activity against a cancer, it is presently very difficult for clinicians anticipate which CAR may display therapeutic activity against a given cancer or subtype of cancer. Due to the significant therapeutic potential of adoptive T cell transfer, there is a clear need for improved methods for identifying and generating new CARs.